Corticotropin-releasing factor type-2 receptor and corticotropin-releasing factor-binding protein coexist in rat ventral tegmental area nerve terminals originated in the lateral hypothalamic area

Eur J Neurosci. 2016 Jan;43(2):220-9. doi: 10.1111/ejn.13113. Epub 2015 Nov 28.

Abstract

There is significant functional evidence showing that corticotropin-releasing factor type-2 receptor (CRF2R) and corticotropin-releasing factor-binding protein (CRF-BP) regulate glutamatergic synapses onto ventral tegmental area (VTA) dopaminergic neurons. It has been shown that CRF requires CRF-BP to potentiate N-methyl-D-aspartate receptors in dopaminergic neurons through CRF2R, and that increases glutamate release in cocaine-treated rats through the activation of CRF2R only by agonists with high affinity to CRF-BP. Furthermore, this CRF-mediated increase in VTA glutamate is responsible for stress-induced relapse to cocaine-seeking behaviour. However, there is a lack of anatomical evidence to explain the mechanisms of CRF actions in VTA. Thus, it was studied whether CRF2R and CRF-BP are expressed in VTA nerve terminals, using a synaptosomal preparation devoid of postsynaptic elements. The current results show that both proteins are co-expressed in glutamatergic and γ-aminobutyric acid (GABA)ergic VTA synaptosomes. A main glutamatergic input to the VTA that has been associated to addictive behaviour is originated in the lateral hypothalamic area (LHA). Thus, this study was focused in the LHA-VTA input using orexin as a marker of this input. The results show that CRF2R and CRF-BP mRNA and protein are expressed in the LHA, and that both proteins are present in orexin-positive VTA synaptosomes. The results showing that CRF2R and CRF-BP are expressed in the LHA-VTA input give anatomical support to suggest that this input plays a role in stress-induced relapse to cocaine-seeking behaviour.

Keywords: VGLUT1; VGLUT2; orexin; synaptosomes; syntaxin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Carrier Proteins / metabolism*
  • Glutamic Acid / metabolism
  • Hypothalamic Area, Lateral / metabolism*
  • Male
  • Neurons / metabolism*
  • Orexins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Synapses / metabolism*
  • Synaptosomes / metabolism
  • Ventral Tegmental Area / metabolism*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • CRF receptor type 2
  • Carrier Proteins
  • Orexins
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • corticotropin releasing factor-binding protein
  • Glutamic Acid
  • gamma-Aminobutyric Acid